Abstract
BACKGROUND: Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who failed bispecific antibody (BsAb) therapy face an extremely poor prognosis, necessitating exploration of effective salvage strategies. This study aimed to evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in this population. METHODS: We retrospectively enrolled 12 consecutive R/R DLBCL patients who received CAR-T therapy after BsAb failure at Beijing Tongren Hospital, Capital Medical University, between July 2023 and February 2025.Clinical data were reviewed to evaluate efficacy and safety outcomes. RESULTS: The 12 patients (M: F = 6:6) had a median age of 53 years (range: 34–65), a median IPI of 3 (range: 1–5), and with a median of 5 prior lines of therapy (range: 1–8). The majority (91.7%, 11/12) had ≥ 2 extranodal sites, and 25% (3/12) had bulky disease (> 7.5 cm). Prior to CAR-T, 33.3% (4/12) were bispecific antibody-relapsed and 66.7% (8/12) were bispecific antibody-refractory. BsAb targets included CD3/CD20 (n = 9; commercial glofitamab n = 7, investigational n = 2) and CD3/CD19 (n = 3, investigational). CAR-T products were CD19/CD22 dual-target (n = 10) and CD19 single-target (n = 2). The median washout period from last BsAb to lymphapheresis was 42 days (range: 8–172).With a median follow-up of 9.3 months (range: 5.3–14), the best overall response rate was 100% (complete response 50%, partial response 50%).Median progression-free survival (PFS) and overall survival (OS) were not reached. The Kaplan-Meier estimates showed 12-month PFS and OS rates were 54.5% and 50.5%, respectively.Cytokine release syndrome occurred in 83.3% (all grade 1–2) and ICANS in 8.3%(all grade 1). Hematologic toxicities were frequent, with grade ≥ 3 neutropenia (100%), anemia (33.3%), and thrombocytopenia (33.3%). Non-hematologic toxicities included grade 1 AST/ALT elevations (33.3%) and coagulation abnormalities (elevated D-dimer 41.7%; grade ≥ 3 hypofibrinogenemia 16.7%). All adverse events were manageable with standard interventions, and no treatment-related deaths occurred. CONCLUSION: CAR-T salvage therapy demonstrated high response rates and manageable safety in BsAb R/R DLBCL patients. Early survival data suggest promising clinical benefit in this high-risk population of BsAb-resistant patients, though extended follow-up is needed to confirm durability. This study provides supporting evidence for CAR-T as a potential salvage strategy in this setting.